Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation.
Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation.
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DOI：
10.1084/jem.20041457
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发表时间：
2004-10-18
期刊：
影响因子：
--
通讯作者：
Bevan MJ
中科院分区：
文献类型：
--
作者：
Gallegos AM;Bevan MJ
胸腺髓质上皮细胞（Mtecs）在胸腺内表达组织特异性抗原（tsa）导致自身反应性T细胞的缺失。然而，由于已知Mtec是抗原呈递细胞（APCs），无法耐受普遍存在的抗原，而且很少Mtec表达给定的TSA，因此尚不清楚对TSA的中枢耐受是由Mtec抗原呈递直接诱导的，还是由胸腺骨髓（BM）源细胞通过交叉呈递间接诱导的。我们发现专业的bm衍生apc从Mtecs获得tsa，并删除自身反应性CD8和CD4 T细胞。虽然Mtec的直接抗原呈递并没有删除本研究中测试的CD4 T细胞群，但Mtec的呈递有效地删除了CD8 T细胞的单克隆和多克隆群体。对于发育中的CD8 T细胞，bm来源的APC和Mtec呈递导致的CD8 T细胞缺失突然发生在过渡性、cd4高CD8低tcr的中间阶段，可能是细胞从皮层向髓质转移的过程。这些研究揭示了Mtecs和bm来源的细胞在胸腺消除自身反应性T细胞中的合作关系。尽管Mtecs合成tsa并删除一部分自身反应性T细胞，但bm来源的细胞通过从Mtecs中捕获的交叉呈递抗原扩大了克隆缺失的范围。
Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs.
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影响因子：
30.5
作者：
McGargill, MA;Derbinski, JM;Hogquist, KA
通讯作者：
Hogquist, KA
DOI：
10.1084/jem.20030413
发表时间：
2003-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avichezer D;Grajewski RS;Chan CC;Mattapallil MJ;Silver PB;Raber JA;Liou GI;Wiggert B;Lewis GM;Donoso LA;Caspi RR
通讯作者：
Caspi RR
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
64.8
作者：
Alam, SM;Travers, PJ;Gascoigne, NRJ
通讯作者：
Gascoigne, NRJ
影响因子：
20.3
作者：
Capone, M;Romagnoli, P;van Meerwijk, JPM
通讯作者：
van Meerwijk, JPM